1,2-Epoxybutane → 3-aminopropyl[2-(S)-hydroxy-3-methyl-butyl]phosphinic acid

HRID 729165Notes

Reaction equation

HRID 729165 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][P:5]([OH:7])[OH:6].[O:8]1[CH:10]([CH2:11][CH3:12])[CH2:9]1.[CH3:13][Si](C)(C)N[Si](C)(C)C>Cl.ClCCl.CCOCC.[I-].[Zn+2].[I-]>[NH2:1][CH2:2][CH2:3][CH2:4][P:5]([CH2:9][C@@H:10]([OH:8])[CH:11]([CH3:12])[CH3:13])(=[O:7])[OH:6]

Participants

8

Reactant 3

HCID 78341,2-EpoxybutaneHCID 13838HexamethyldisilazaneHCID 99892683-Amino-propanephosphonous

Product 1

HCID 186451683-aminopropyl[2-(S)-hydroxy-3-methyl-butyl]phosphinic acid

Reagents, catalysts & solvents 4

HCID 9883512zinc(II)iodideCatalystHCID 313Hydrochloric AcidSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

A suspension of 2.46 g of 3-aminopropylphosphonous acid in 20 ml of hexamethyldisilazane is heated to reflux under an inert gas for 24 hours after which a clear solution results. The excess hexamethyldisilazane is removed by distillation at atmospheric pressure under a slight positive pressure of inert gas to afford a colourless oil. The oil is cooled to circa 40° and treated with 0.64 g of anhydrous zinc iodide and 25 ml of (S)-(+)-1,2-exoxy-3-methyl-butane. An exothermic reaction occurs andthe epoxybutane refluxes. Reflux is continued for 6 hours after which time thin layer chromatography indicates the reaction to be complete. The reaction mixture is filtered and the filtrate evaporated to dryness in vacuo at 40°. The residue is dissolved in water and stirred at roomtemperature for 1 hour and the water removed in vacuo to give an oily solid. This is dissolved in some 2.0M aqueous hydrochloric acid and washedwith dichloromethane and ether. Removal of the water at 40° in vacuoaffords a brown solid which is purified by ion-exchange chromatography on DOWEX® 50 W×8 (14-40 mesh) to give 3-aminopropyl[2-(S)-hydroxy-3-methyl-butyl]phosphinic acid, m.p. 187°-189°, [α]D20 =-14.5°.

Workup

  1. temperatureis heated
  2. temperatureto reflux under an inert gas for 24 hours after which a clear solution
  3. customresults
  4. customThe excess hexamethyldisilazane is removed by distillation at atmospheric pressure under a slight positive pressure of inert gas
  5. customto afford a colourless oil
  6. temperatureThe oil is cooled to circa 40°
  7. customAn exothermic reaction
  8. temperatureReflux
  9. customthe reaction
  10. filtrationThe reaction mixture is filtered
  11. customthe filtrate evaporated to dryness in vacuo at 40°
  12. dissolutionThe residue is dissolved in water
  13. customthe water removed in vacuo
  14. customto give an oily solid
  15. customRemoval of the water at 40° in vacuoaffords a brown solid which
  16. customis purified by ion-exchange chromatography on DOWEX® 50 W×8 (14-40 mesh)

Sources & evidence

ORD record
ord-691d4ba0d5bc4e87a12768f2ab0ecc65
Source dataset
uspto-grants-1991_09
Patent number
US05051524

Reaction notes

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